Figure 9. Mec1‐S1991 phosphorylation limits transcription during replication stress.

Upon HU‐induced replication stress, Mec1^ATR and Rad53 are activated through phosphorylation, including phosphorylation at Mec1‐S1991. Mec1‐S1991 phosphorylation is not required to activate the downstream checkpoint effector kinase Rad53, yet it promotes the attenuation of RNAPII‐ and RNAPIII‐mediated transcriptions during replication stress, acting on a variety of transcription controlling factors. Proteasome‐mediated RNAPII degradation during replication stress requires a functional Cul3‐Elc1 ubiquitin ligase. RNAPIII is evicted in a Mec1‐dependent manner but not degraded. Mec1‐induced RNAPII removal from chromatin allows the release of highly transcribed genes from nuclear pore under HU stress, while Rad53 is thought to act directly on the nuclear pore complex (NPC).